Unraveling the complexity of atopic dermatitis: The CK‐CARE approach toward precision medicine

Abstract

Although clinicians acknowledge the phenotypic heterogeneity of atopic dermatitis (AD), its current management remains a “one-size-fits-all” approach. Even the newest approved medicinal products and those in the pipeline ground on the assumption of a single or dominant underlying mechanism which are mainly based on two pillars: (a) intrinsically disturbed epidermal barrier function as the result of numerous candidate genes related to the biochemical structure of the epidermis such as Filaggrin-1 or 2, Claudin-1, and many others; (b) the assumed dominant T2 type of immune response locally mainly involving IL-13 and IL-31. Recent reports exploring the immunologic background unraveled different immune responses in various ethnic populations1 and between pediatric and adult patients.2 We begin to understand the mechanisms behind the complexity of AD. Substantial hurdles in translating this emerging knowledge into personalized prevention and therapeutic strategies toward precision medicine remain.3 Overcoming these hurdles is a major task for academic research which has access to large and representative cohorts. In this letter, (a) we expose the gaps in our understanding of the complexity of AD and (b) describe the approach chosen by the Christine Kühne-Allergy Research and Education (CK-CARE) program. In a joint academic effort to address these gaps, a unique patient-centric project was started with the support of the Kühne Foundation: The CK-CARE registry and biobank program with currently more than 1200 patients recruited under real-world conditions. The CK-CARE program aims (a) to explore the mechanisms underlying the heterogeneity of AD and its various trajectories; (b) to identify and validate biomarkers of different values (diagnostic, prognostic, predictive, etc) for patient stratification in patient care, clinical trials, and research projects10; (c) to identify new potential drug targets; (d) to collect and learn from real-world data; and (e) to develop and provide tools for drug development programs in the era of precision medicine. We are far from understanding the mechanistic complexity of the AD puzzle. With the analysis of comprehensive sets of patient information and biomaterial, the CK-CARE program will contribute to the discovery and validation of relevant biomarkers and pave the way to precision medicine in AD. This study was supported by the Christine Kühne—Center for Allergy Research and Education (CK-CARE). TB reports personal fees from Sanofi/Genzyme/Regeneron, AbbVie, Allmiral, AnaptysBio, Arena Pharma, Asana Biosciences, Böhringer-Ingelheim, Celegne, Dermavant, DermTreat, FLX Bio, Galapagos, Galderma, GSK, Incytes, Kymab, LEO, Lilly, MenloTx, Novartis, Pfizer, UCB, and Vectans. C T-H has received grants or personal fees from Sanofi Genzyme, Töpfer, Sebapharma, Novartis, Lilly Pharma, Danone Nutricia, outside the submitted work. GS has no conflict of interest to declare. RL is part of the advisory board of Pfizer, Vifor, AstraZeneca, Milupa, Sanofi Genzyme, Menarini, and has received fees for a talk in the Forum für Medizinische Fortbildung. CA declares research funding from Allergopharma, Idorsia, Swiss National Science Foundation, European Commission's Horizon 2020 Framework Programme (Cure), Novartis Research Institutes, AstraZeneca, Scibase, and Sanofi Aventis Regeneron. CA also serves on the advisory board of SciBase. P S-G reports grants or personal fees from AbbVIe, Astra Zeneca, BioMed, Eli Lilly, Galderma, GSK, LEO, Novartis, Pfizer and Sanofi/Genzyme/Regeneron.

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